Solute absorption from the airways of the isolated rat lung. III. Absorption of several peptidase-resistant, synthetic polypeptides: poly-(2-hydroxyethyl)-aspartamides.
A series of samples of the synthetic polypeptide poly-alpha, beta-[N(2-hydroxyethyl)-DL-aspartamide] (PHEA), containing covalently bound fluorophore, ethylcarbonyl-6-aminofluorescein, and exhibiting different molecular weight distributions with weight average molecular weights ranging from approximately 4 to 43 kD, was prepared and characterized. Aqueous solutions of the polymers were administered to the airways of isolated perfused rat lung preparations, and transfer to the perfusate was measured. Polymers administered directly to the perfusate were not degraded during the experiment. Polymer transfer rates were dependent upon starting molecular weight distribution, larger molecules being absorbed more slowly. In the case of a polymer with a median molecular weight of 7.2 kD, the absorbed species appeared to be smaller molecules than those which were originally administered. This was not the case for a 3.98-kD polymer; absorbed material had a gel permeation chromatography elution volume equivalent to that of the administered material. Absorption for the 3.98-kD polymer was found to be dose dependent. Approximately 70% absorption of a 0.2-mg dose occurred in 100 min. Much larger polymers (up to 11.65 kD) were also absorbed at finite rates. Results are discussed in the context of macromolecular delivery to the systemic circulation via the lung.
Niven
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RW
Department of Environmental Science & Physiology, Harvard University, Boston, Massachusetts 02115.
Rypacek
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F
Byron
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PR
D000042:Absorption; D000818:Animals; D004355:Drug Stability; D005452:Fluoresceins; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats
D005452:Fluoresceins; D005456:Fluorescent Dyes; D010455:Peptides; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); C025247:N-(2-aminoethylcarbonyl)-5(6)-aminofluorescein